1. Field of the Invention
This invention relates to a composition containing a tissue plasminogen activator. Namely, this invention is available in medical fields. More particularly, it relates to a composition which has been invented for an improved application of a tissue plasminogen activator, which is employed to treat various circulatory diseases caused by thrombosis, to medical fields. 2. Description of Prior Arts
According to custom, tissue plasminogen activator will be hereinafter abbreviated as tPA.
It is well known that thrombi can be dissolved by adenolysis with the use of a group of compounds called tissue plasminogen activators to thereby relieve circulatory disorders caused thereby. That is to say, active plasmin formed by a plasminogen activator destroys fibrin network and dissolves the same. Conventionally available plasminogen activators for therapeutic uses include streptokinase and urokinase. However these compounds are not specific to thrombi but may sometimes destroy not only fibrin but also blood proteins such as fibrinogen, prothrombin and factors V and VIII accompanied by some side effects including internal hemorrhage. Therefore streptokinase and urokinase are directly administered to a thrombus via a catheter, which requires a troublesome procedure. Thus the administration of those compounds has been on the decline. On the other hand, there are some plasminogen activators extracted from normal and cancerous tissues. These plasminogen activators are classified into urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), which relates to the present invention, depending on the origins.
It is known that tPA is therapeutically useful since it has a much higher affinity for fibrin than uPA does. Thus it has been urgently required to establish a pharmaceutical technique to fully utilize the excellent therapeutic effect of tPA as described above.
Since, however, tPA is a protein hardly soluble in water, it is very difficult to formulate the same into an aqueous preparation such as an injection. It is the most serious problem in the practical application of tPA in medical fields. tPA should be directly administered to the circulatory system so that it can not be practically applied unless thoroughly solubilized in water. However there has been no satisfactory technique for the dissolution of tPA in water. Prior art concerning a tPA preparation includes the one disclosed in Japanese Patent Laid-Open No. 196824/1984. However the problem of the dissolution of tPA in water is not solved thereby.